Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “SPIRONOLACTONE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources
PubMed1982

Treatment of hirsutism with spironolactone.

Clinical and endocrine evaluations of 39 patients with hirsutism were performed to determine the effectiveness and site(s) of action of an antiandrogenic compound, spironolactone. Treatment with spironolactone at a dose of 200 mg/day resulted in a clear beneficial effect on the quantity and quality of facial hair growth in 19 of 20 patients with moderate to severe hirsutism. Regression of hirsutism in terms of diameter, density, and the rate of facial hair growth was noticeable within two months. The maximal effect was observed at six months and was maintained at 12 months of treatment. Spironolactone was equally effective in reducing hirsutism in women with polycystic ovary syndrome and idiopathic hirsutism. These clinical observations were associated with a prompt and sustained reduction in levels of androgen of ovarian origin without affecting levels of adrenal androgen and cortisol. Apart from diuresis, which was limited to the first few days of treatment, there were no discernible side effects the one year of this study. Our results indicate that spironolactone is a highly effective and safe agent for the treatment of hirsutism through its inhibitory action on both ovarian androgen secretion and peripheral androgen action.

Amenorrhea↗
PubMed1982

Antagonism of aldosterone in normal subjects by Ro 12-2503 and spironolactone.

The potency and efficacy of a single dose of a new aldosterone antagonist, potassium 17 a-hydroxy-6 beta, 7 beta-methylene-3-oxo-D-homo-17a alpha-pregna-4,16-diene-21-carboxylate (Ro 12-2503), in reversing the renal effects of exogenous aldosterone were compared to those of spironolactone, and placebo. The study was performed according to double-blind and crossover procedure in six healthy male subjects. Both drugs, spironolactone and Ro 12-2503, did not completely antagonize the effects of aldosterone. The efficacy of Ro 12-2503 in terms of the urinary Na+/K+ ratio and the urinary Na+ concentration was less than that of spironolactone. Spironolactone produced a slightly greater natriuresis, but the difference was not significant. The method described, based on standard bioassay techniques permits a comparison of the two drugs, and may prove useful in the screening and evaluation of aldosterone antagonists.

Adult↗
PubMed1980

Modifications of bile secretion and liver microsomal enzymes by aldosterone and spironolactone.

During a period of two weeks male adult albino rabbits received a daily subcutaneous injection of: Group I: 0.1 ml of 0.9% sodium chloride solution/kg b. wt (control); Group II: 150 micrograms spironolactone/kg b. wt. Twenty-four hours after the final injection, the animals were anesthesized, the bile duct was cannulated (after ligation of the cystic duct) and bile was collected for two hours. At the end of the experiment, the liver was removed, weighed and submitted for cytochrome P-450 measurement and microscopic analyses. Red blood cell sodium content was measured in the aldosterone group before and after treatment. Compared with control animals, we found the following: (I) The bile flow, the biliary sodium and bile acid excretion were significantly decreased (P less than 0.01) in aldosterone-treated animals and significantly increased (P less than 0.01) in spironolactone treated ones. (II) In animals treated with aldosterone and in those treated with spironolactone, liver cytochrome P-450 was significantly increased (P less than 0.001). (III) In livers of both aldosterone and spironolactone-treated animals, there were hyaline changes in the hepatocytes without necrosis or steatosis. Electron microscope studies revealed a proliferation of smooth endoplasmic reticulum in livers of both groups. (IV) Red blood cell sodium content was significantly increased (P less than 0.001) after treatment with aldosterone. In conclusion, aldosterone and spironolactone have the opposite effect on bile secretion. Both are liver microsomal enzyme inducers. A correlation between bile secretion and liver enzyme induction seems improbable.

Aldosterone↗
PubMed1994

Effect of spironolactone on dimethyl mercury toxicity. A possible molecular mechanism.

The protective activity of spironolactone (CAS 52-01-7) against dimethyl mercury intoxication was studied. Dimethyl mercury increased serum glutamate pyruvate transaminase (SGPT), serum bilirubin, blood urea nitrogen (BUN), and caused impairment of the drug metabolic activity of rat liver in vivo and in vitro. It also caused a severe neuropathy to these animals. Administration of spironolactone caused a reduction of dimethyl mercury toxicity. It decreased the values of SGPT, bilirubin and BUN, and restored the impaired drug metabolism caused by dimethyl mercury. The neuropathy produced after administration of dimethyl mercury was only mildly ameliorated by the treatment with spironolactone. Pregnenolone-16 alpha-carbonitrile (PCN), a potent microsomal enzyme inducer, had only a weak action, with the expected exception of the repair of the impaired drug metabolism of the liver. A mechanism of the protective action of spironolactone against dimethyl mercury intoxication is proposed. It is suggested that both the ability to induce drug metabolizing enzymes, here demethylases, and the capacity to bind to the demethylated metabolite of the organic mercurial, giving a non toxic, easily excretable complex should coexist in the protective molecule.

Alanine Transaminase↗
PubMed1993

Attenuation by spironolactone of the magnesiuric effect of acute frusemide administration in patients with liver cirrhosis and ascites.

The effect of spironolactone on renal magnesium excretion under both basal conditions and conditions of frusemide-induced diuresis was studied in 11 control subjects with normal hepatic and renal function and in 12 patients with liver cirrhosis and ascites. In the control group, oral administration of spironolactone (200 mg daily for 5 days) resulted in a significant decrease in the mean renal excretion of both magnesium and potassium. In the cirrhotic patients, spironolactone did not significantly change the mean renal excretion of magnesium or potassium, but it produced a significant reduction in the frusemide-induced increase in the renal excretion of both potassium and magnesium. The study suggests that spironolactone decreases magnesium excretion in normal subjects and antagonizes the magnesiuric effect of frusemide in patients with liver cirrhosis and secondary aldosteronism.

Adult↗
PubMedDate not supplied

Effect of spironolactone treatment on the ultrastructure of cortical intercalated cells in the rat kidney.

The ultrastructure of intercalated cells in the rat renal cortex was investigated after 7 days of treatment with the mineralocorticoid inhibitor spironolactone. In untreated and treated animals, two subgroups of IC cells (A-IC and B-IC) could be recognized by electron microscopy, but a substantial fraction of IC cells that corresponded to neither A nor B forms, so-called NonA-NonB, was also found. After spironolactone treatment, qualitative and morphometric analyses showed a decrease in volume density of mitochondria, in cell cross-sectional area, and in boundary length of basolateral membranes in A-IC cells. Among the NonA-NonB-IC cells, some revealed especially abundant mitochondria. Although the frequency of NonA-NonB-IC cells did not change significantly, these mitochondria-rich cells appeared with increased frequency after spironolactone treatment. The ultrastructural changes in A-IC cells might reflect a direct effect of spironolactone on the A-IC cells. However, it is also conceivable that the changes are secondary to functional alterations induced in neighboring segment-specific cells by the experimental conditions.

Animals↗
PubMed1962

Metabolic studies on patients with resistant heart failure treated by spironolactone.

Metabolic balance studies were carried out on five patients with resistant heart failure treated with spironolactone and other diuretics. Spironolactone alone had little effect. When it was used in a daily dose of 400-600 mg. in combination with hydrochlorothiazide 100 mg. daily, the results were excellent in two patients. One of these was still free of failure after 12 months on combined therapy. In the other patient the serum potassium became elevated after a good diuresis, though on subsequent intermittent therapy with the drug the patient remained well for 12 months. In two other patients administration of spironolactone had to be discontinued because of elevation of the serum potassium before a good diuresis could take place. The fifth patient died.Spironolactone can be a useful adjunct to the therapy of resistant heart failure, but there appears to be a real danger of causing the serum potassium to rise to toxic levels in patients so treated.

Diuresis↗
PubMed1963

EFFECT OF AN ALDOSTERONE ANTAGONIST (SPIRONOLACTONE) ON PATIENTS WITH SEVERE CONGESTIVE HEART FAILURE.

Spironolactone was evaluated as a diuretic in the therapy of six patients with chronic severe congestive heart failure, during which metabolic balance studies were performed. Two of the patients showed a clear-cut although moderate diuresis and natriuresis in response to spironolactone in the presence of other diuretics. Two patients had slight unsustained responses and two showed no response. No significant change in potassium excretion was observed. A decrease in the serum sodium level was noted in four patients, associated with a rise in serum potassium. Urinary aldosterone excretion was normal or low in all patients and showed no correlation with the diuretic response to spironolactone.It is concluded that spironolactone has definite but limited usefulness in the therapy of some but not all patients with chronic congestive heart failure.

Aldosterone↗
PubMed1975

Relative potency of prorenoate and spironolactone in normal man.

The potency of single doses of a new aldosterone antagonist, prorenoate, in reversing the renal effects of the synthetic mineralocorticoid fludrocortisone was compared to that of spironolactone in a double-blind balanced crossover study in 12 healthy subjects. The potency of prorenoate potassium as related to elevation of the urinary log 10 10 Na/K ratio (2.69:1) and as related to potassium retention (3.75:1) was significantly higher than that of spironolactone. Prorenoate produced greater natriuresis (1.64:1) but the difference was not significant. There was evidence for a qualitative difference between spironolactone and prorenoate; the latter significantly more potent in retaining potassium than in increasing sodium excretion. The simple methodology described is based on standard bioassay principles, yielded a valid and sensitive comparison of the two drugs, and should prove useful in the evaluation of other aldosterone antagonists.

Adolescent↗
PubMed1977

Enhancement by food of canrenone bioavailability from spironolactone.

The influence of food intake on the bioavailability of canrenone, the major and active metabolite of spironolactone, was explored in 8 healthy male volunteers. Spironolactone was administered as a single oral dose of 100 mg, both in the fasting state and together with a standardized breakfast. Numerous venous blood samples were taken from 30 min to 96 hr after ingestion of the drug, and the plasma concentrations of canrenone were determined by spectrofluorometry. The results indicate that more canrenone enters the general circulation when spironolactone in ingested together with a meal.

Administration, Oral↗
PubMed1994

Effects of low-sodium diet and spironolactone on portal pressure in patients with compensated cirrhosis.

The aim of this study was to investigate the hemodynamic effects of spironolactone associated with a low-sodium diet (n = 14) or a low-sodium diet alone (n = 9) in patients with compensated cirrhosis and portal hypertension. Spironolactone significantly reduced the plasma volume. This effect was associated with a significant reduction in the hepatic venous pressure gradient, from 17.6 +/- 3.6 mm Hg to 15.3 +/- 3.5 mm Hg (-13% +/- 13%; p < 0.01). Azygos blood flow (-20% +/- 20%), cardiac output (-16.2% +/- 10.5%) and mean arterial pressure (-9% +/- 9%) also decreased significantly. However, there were no significant changes in hepatic blood flow. Patients receiving low-sodium diet alone experienced a mild but significant reduction in hepatic venous pressure gradient (-6.3% +/- 6%) and in mean arterial pressure (-4% +/- 5%). There were no significant changes in cardiac output and in hepatic or azygos blood flows. This study indicates that low-sodium diet plus administration of spironolactone reduces portal pressure and azygos blood flow in patients with compensated cirrhosis. Low-sodium diet alone only produces mild effects that are likely to be clinically irrelevant.

Aged↗
PubMed1977

Spironolactone: relationship between concentrations of dethioacetylated metabolite in human serum and milk.

The concentration of canrenone, a principal metabolite of spironolactone, was determined in human serum and milk. The milk to serum concentration ratios of this metabolite were 0.72 at 2 hr and 0.51 at 14.5 hr after ingestation of spironolactone. It was estimated that the maximum quantity of canrenone ingested daily by a human infant via its mother's milk would be approximately 0.2% of the daily dose of spironolactone given to the mother.

Adult↗
PubMed1978

Stability-indicating methods for quantitative determination of spironolactone using high-pressure liquid chromatography and blue tetrazolium reaction.

Stability-indicating methods for the quantitative determination of spironolactone were developed. The methods are based on high-pressure liquid chromatography and a reaction with blue tetrazolium. Both methods are accurate, precise, and sensitive and gave excellent results with commercial tablets, including those containing hydrochlorothiazide in addition to spironolactone, The blue tetrazolium method cannot be used in the presence of high concentrations of either polyethylene glycols or water. Spironolactone decomposition in water or polyethylene glycol appears to follow pseudo-first-order kinetics. The decomposition constant at 65 degrees was 0.0253/day in water versus 0.115/day in polyethylene glycol ointment base USP.

Chromatography, High Pressure Liquid↗
PubMed1991

Preformulation studies of spironolactone: effect of pH, two buffer species, ionic strength, and temperature on stability.

Using a stability-indicating HPLC assay method, the effect of pH, two buffer species (citrate and phosphate), ionic strength, and temperature on the stability of spironolactone in 20% solution of ethyl alcohol in water has been studied. The optimum pH of stability appears to be approximately 4.5. On increasing the buffer concentration, both species hastened the decomposition of spironolactone. The ionic strength did not affect the stability of the drug. The energy of activation has been estimated to be approximately 78.8 kJ/mol at pH 4.3. The un-ionized spironolactone is subject to general acid-base catalysis. The Kh and Koh values at 40 degrees C have been estimated to be 1.63 and 2.8 x 10(5) day-1, respectively. The HPO4(-2) ion had approximately 10 times more catalytic effect than the H2PO4(-1) ion. This data will be used to develop a stable oral liquid dosage form of the drug.

Buffers↗
PubMed1978

Effects of furosemide and spironolactone on the behavior of morphine-tolerant rats.

In morphine-tolerant rats, a reappearance of morphine catalepsy and a disappearance of the turning behavior characteristic of brain-lesioned tolerant animals were observed under the influence of furosemide and spironolactone. The administration of spironolactone together with daily morphine treatment resulted first in an intensification of the morphine symptoms as measured by catalepsy and a retarded appearance of tolerance, typically characterized by a shift from catalepsy to turning movements in animals with single-sided brain lesions. Nontoxic doses of spironolactone raised the sensitivity of morphine-tolerant rats so that previously tolarated morphine doses become lethal.

Animals↗
PubMed1978

Increased digitoxin cleavage by liver microsomes of spironolactone-pretreated rats.

Pretreatment of rats with spironolactone caused an fourfold increased cleavage rate of the sugar chain of digitoxin (dt-3) in vitro yielding digitoxigenin-bis-digitoxoside. This was due to an enhanced, cyt. P450 dependent, formation of 15'-dehydro-dt-3, the intermediate which has to be formed before the terminal sugar can be split off. The second reaction catalysed by microsomal monoxygenases, the 12-beta-hydroxylation, was only increased by a factor 2. In contrast to the effects of spironolactone no increase of metabolism could be observed after phenobarbital pretreatment. From our results it may be concluded that the enhanced dt-3 metabolism in vivo is mainly caused by spironolactone inducible monoxygenases which catalyse the oxidation of the terminal sugar.

Animals↗
PubMed1976

Pharmacokinetics of spironolactone in man.

Five healthy male volunteers received 500 mg Aldactone orally together 100 muCi 3H-20-21-spironolactone; one elderly patient received 1 mCi 3H-spironolactone without additional 'cold' drug. For 6 days the disposition kinetics of the drug were studied in plasma, urine and feces. The tritium concentrations in plasma reached a peak between 25-40 min after administration amounting to 2-3% of the dose/1. Up to the 12th h, they fell rapidly and showed a monoexponential decline (t 1/2: 2.57 +/- 0.27 days) between the 36th and 96th h. Later, a striking increase in the speed of elimination of radioactivity from plasma (t 1/2: 1.66 +/- 0.21 days) was observed. The biological half-life of labeled material in plasma was longer than that of fluorigenic compounds. 47-57% of the dose were excreted in urine and the remaining amount could be detected in feces (total recovery 90%). The half-life of the urinary excretion rate was distinctly shorter (t 1/2: 0.9 +/- 0.11 days) than that of total radioactivity in plasma. This, together with an observed increase of the polar fraction in urine from 35 up to 85%, which was accompanied by a decrease in plasma from 55 to 35%, suggests either tubular reabsorption or enterohepatic recirculation of lipophilic compounds. TLC-separation of the lipophilic fraction in urine revealed two previously unknown compounds of which the main congener was identified as 3-(3-oxo-7 alpha-methylsulfonyl-6 beta, 17 beta-dihydroxy-4-androsten-17 alpha-yl) propionic acid gamma-lactone, as well as canrenone and the metabolites which have already been described (Karim and Brown, 1972; Karim et al., 1975). This metabolite represents the main lipophilic degradation product in urine within the first hours, whereas the 6 beta-OH-7 alpha-methylsulfinyl-spirolactone leveled off and seemed to be and endexcretion product. For further characterisation, the polar fraction was subjected to acidic hydrolysis. The known metabolic pathways of spironolactone degradation are discussed.

Administration, Oral↗
PubMed1988

The effect of renal and hepatic impairment and of spironolactone on digoxin immunoassays.

The effect of renal and/or hepatic dysfunction, and of concomitant spironolactone therapy, on seven commercial digoxin assays was evaluated in 45 patients taking both these drugs, and a comparison made with the digoxin concentrations measured using the same assays in 30 patients taking digoxin in the absence of spironolactone. The study showed that increasing renal dysfunction resulted in increasing inaccuracy in assay results with the methods tested. The influence of concomitant spironolactone was to produce a further distortion, which was shown to be additive in patients with impaired renal and/or liver function. The results highlight the unresolved specificity problems which persist in many, if not all, of the immunoassays currently offered to clinical laboratories which, if not recognised, could significantly influence digoxin therapy and patient management.

Aged↗